PMID- 31334344
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220409
IS  - 2373-8731 (Print)
IS  - 2373-8731 (Electronic)
IS  - 2373-8731 (Linking)
VI  - 5
IP  - 7
DP  - 2019 Jul
TI  - Complement Markers in Blood and Urine: No Diagnostic Value in Late Silent 
      Antibody-Mediated Rejection.
PG  - e470
LID - 10.1097/TXD.0000000000000915 [doi]
LID - e470
AB  - BACKGROUND: Antibody-mediated rejection (AMR) is a major cause of kidney 
      allograft failure. Its molecular mechanisms are multifaceted and may include a 
      role of complement activation via the classical pathway. Here, we investigated 
      whether noninvasive complement monitoring adds predictive power to the diagnosis 
      of AMR in the setting of donor-specific antibody (DSA) positivity. METHODS: In 
      this cross-sectional study, 741 kidney transplant recipients with stable graft 
      function >/=180 days posttransplantation were screened for the presence of human 
      leukocyte antigen (HLA) alloantibodies. Eighty-three of 111 DSA-positive 
      recipients underwent protocol biopsies and were tested for blood and urinary 
      levels of complement proteins (C1q, C4, C3) and activation products (C4d, C3a, 
      C5a, C5b-9). RESULTS: Forty-seven recipients were diagnosed with AMR, and 21 were 
      C4d-positive. While biopsy-confirmed AMR (and C4d) associated with DSA-binding 
      strength (IgG mean fluorescence intensity of the immunodominant DSA versus AMR; 
      area under the receiver operating characteristic curve: 0.76), tested complement 
      markers did not have any predictive value for rejection (area under the receiver 
      operating characteristic curve: 0.49-0.56). There were, however, tight 
      correlations between complement activation products in urine and 
      protein/creatinine ratio (rho = 0.44-0.64; P < 0.001). Analysis of death-censored 
      graft survival over a median of 60 months revealed no independent associations 
      with levels of complement markers in blood or urine. CONCLUSIONS: Complement 
      patterns in blood and urine failed to identify AMR in late biopsies and may have 
      no relevant diagnostic value in this particular context.
FAU - Mezo, Blanka
AU  - Mezo B
AD  - IIIrd Department of Internal Medicine and MTA-SE Research Group of Immunology and 
      Hematology, Research Laboratory, Hungarian Academy of Sciences and Semmelweis 
      University, Budapest, Hungary.
FAU - Heilos, Andreas
AU  - Heilos A
AD  - Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 
      Vienna, Austria.
FAU - Bohmig, Georg A
AU  - Bohmig GA
AD  - Division of Nephrology and Dialysis, Department of Medicine III, Medical 
      University of Vienna, Vienna, Austria.
FAU - Eskandary, Farsad
AU  - Eskandary F
AD  - Division of Nephrology and Dialysis, Department of Medicine III, Medical 
      University of Vienna, Vienna, Austria.
FAU - Wahrmann, Markus
AU  - Wahrmann M
AD  - Division of Nephrology and Dialysis, Department of Medicine III, Medical 
      University of Vienna, Vienna, Austria.
FAU - Bond, Gregor
AU  - Bond G
AD  - Division of Nephrology and Dialysis, Department of Medicine III, Medical 
      University of Vienna, Vienna, Austria.
FAU - Kozakowski, Nicolas
AU  - Kozakowski N
AD  - Department of Clinical Pathology, Medical University of Vienna, Vienna, Austria.
FAU - Halloran, Philip F
AU  - Halloran PF
AD  - Alberta Transplant Applied Genomics Centre, ATAGC, University of Alberta, 
      Edmonton, AB, Canada.
FAU - Rusai, Krisztina
AU  - Rusai K
AD  - Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 
      Vienna, Austria.
FAU - Prohaszka, Zoltan
AU  - Prohaszka Z
AD  - IIIrd Department of Internal Medicine and MTA-SE Research Group of Immunology and 
      Hematology, Research Laboratory, Hungarian Academy of Sciences and Semmelweis 
      University, Budapest, Hungary.
LA  - eng
PT  - Journal Article
DEP - 20190627
PL  - United States
TA  - Transplant Direct
JT  - Transplantation direct
JID - 101651609
PMC - PMC6616143
COIS- The authors declare no conflicts of interest.
EDAT- 2019/07/25 06:00
MHDA- 2019/07/25 06:01
PMCR- 2019/06/27
CRDT- 2019/07/24 06:00
PHST- 2019/05/01 00:00 [received]
PHST- 2019/05/22 00:00 [revised]
PHST- 2019/05/23 00:00 [accepted]
PHST- 2019/07/24 06:00 [entrez]
PHST- 2019/07/25 06:00 [pubmed]
PHST- 2019/07/25 06:01 [medline]
PHST- 2019/06/27 00:00 [pmc-release]
AID - 10.1097/TXD.0000000000000915 [doi]
PST - epublish
SO  - Transplant Direct. 2019 Jun 27;5(7):e470. doi: 10.1097/TXD.0000000000000915. 
      eCollection 2019 Jul.